The direct effect of drugs on parathyroid gland and bone metabolism is being investigated by tissue culture methods. We have recently developed a sensitive radioimmunoassay for gamma PTH to estimate the synthesis and secretion of parathyroid hormone (gamma PTH) by rat parathyroid glands cultured in medium containing radiolabeled amino acids. TCA-precipitable radiolabeled proteins, and bioassay by bone tissue culture of the gland medium are also done. Comparative effect of calcium and magnesium on gamma PTH synthesis and secretion indicate that calcium has the dominant and magnesium has only a transitory and smaller effect on the control of parathyroid gland metabolism. Among the drugs studied in this system, chlorothiazide (10 to the minus 4th power and 10 to the minus 5th power M) and cortisol (10 to the minus 6th power M) stimulated the secretion of gamma PTH in gland cultures and inhibited PTH-stimulated resorption in bone cultures; beta-estradiol (10 to the minus 6th power M) inhibited gamma PTH secretion and had no demonstrable direct effect on bone resorption.